An unusual cause of gynaecomastia in a male

Summary: Beta-human chorionic gonadotropin (βhCG) is normally produced by syncytiotrophoblasts of the placenta during pregnancy and aids embryo implantation. However, it is also secreted in varying amounts in non-pregnant conditions commonly heralding a neoplastic process. We present a case of 50-year-old man, who presented with bilateral gynaecomastia with elevated testosterone, oestradiol, suppressed gonadotropins with progressively increasing levels of human chorionic gonadotropin (hCG). Biochemical and radiological investigations including ultrasonography of testes, breast tissue, MRI pituitary and CT scan full body did not identify the source of hCG. FDG PET scan revealed a large mediastinal mass with lung metastasis. Immunostaining and histological analysis confirmed the diagnosis of primary choriocarcinoma of the mediastinum. It is highly aggressive and malignant tumor with poor prognosis. Early diagnosis and management are essential for the best outcome. Learning Points: High βhCG in a male patient or a non-pregnant female suggests a paraneoplastic syndrome. In the case of persistently positive serum hCG, exclude immunoassay interference by doing the urine hCG as heterophilic antibodies are not present in the urine. Non-gestational choriocarcinoma is an extremely rare trophoblastic tumor and should be considered in young men presenting with gynaecomastia and high concentration of hCG with normal gonads. A high index of suspicion and extensive investigations are required to establish an early diagnosis of extra-gonadal choriocarcinoma. Early diagnosis is crucial to formulate optimal management strategy and to minimize widespread metastasis for best clinical outcome

Hyperparathyroidism in Survivors of Childhood Malignancy after Total Body Irradiation

Objective: The risk of developing hyperparathyroidism (HPT) in adults after radiation exposure is higher than that of the general population. Extensive follow up guidelines of United Kingdom Children’s Cancer Study group (UKCCSG) or Scottish intercollegiate guidelines network (SIGN) do not recommend monitoring serum calcium or parathyroid hormone in patients treated for childhood malignancies. The aim of this study was to examine the occurrence of HPT in a cohort of survivors of childhood malignancy attending a late effects clinic after their treatment for haematological and non-haematological malignancies that included previous irradiation Design and methods: Study was performed in 105 patients attending a late effects clinic. These patients had received different modalities f treatment including surgery, chemotherapy, radiotherapy and bone marrow transplant for haematological and non-haematological malignancies in their childhood with. All patients had evaluation for thyroid and parathyroid disease with a clinical examination and biochemical investigations. Patients with hyperparathyroidism were treated with parathyroidectomy in the absence of thyroid disease and positive localization on imaging. This resulted in normalization of serum calcium. Conclusion: This data suggests that there is a significant risk of hyperparathyroidism in young females with haematological malignancies who received total body irradiation as a single fraction for bone marrow transplant

Molecular Identification of Eimeria Species in Broiler Chickens in Trinidad, West Indies

Coccidiosis is an intestinal disease of chickens of major economic importance to broiler industries worldwide. Species of coccidia found in chickens include Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis, Eimeria necatrix, Eimeria praecox, and Eimeria tenella. In recent years, polymerase chain reaction (PCR) has been developed to provide accurate and rapid identification of the seven known Eimeria species of chickens. The aim of this study was to use species-specific real-time PCR (qPCR) to identify which of the seven Eimeria species are present in Trinidad poultry. Seventeen pooled fecal samples were collected from 6 broiler farms (2–5 pens per farm) across Trinidad. Feces were also collected from birds showing clinical signs of coccidiosis in two live bird markets (pluck shops). qPCR revealed the presence of five species of Eimeria (E. acervulina, E. maxima, E. mitis, E. necatrix, and E. tenella), but not E. brunetti or E. praecox. Mixed infections were detected on all broiler farms, and DNA of two highly pathogenic Eimeria species (E. tenella and E. necatrix) was detected in feces taken from clinically sick birds sampled from the two pluck shops

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia

BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. METHODS: To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. RESULTS: Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPβ target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. CONCLUSIONS: These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting.R01 AR060217 - NIAMS NIH HHS; R01 AR060209 - NIAMS NIH HHS; T32 HD043730 - NICHD NIH HHS; R00 HL098453 - NHLBI NIH HHS; R00HL098453 - NHLBI NIH HHS; R01AR060209 - NIAMS NIH HHS; R01AR060217 - NIAMS NIH HH

Glucagon Secreting Tumors and Glucagonoma Syndrome

Glucagonomas are the functioning neuroendocrine tumors. These arise from pancreatic islet α-cells. These tumors are extremely rare and have an annual incidence of 1 per 20-40 million population 80% of glucagon-expressing tumors are sporadic, and 20% are associated with genetic syndromes such as Multiple Endocrine Neoplasia-type 1. Glucagonoma typically occurs in the distal pancreas, and around 85% are in the body or tail. It tends to be large at the time of diagnosis. Most reported cases of glucagonoma are malignant and about 65-75% patients present with metastatic disease. The liver is usually the first site of metastases, followed by the involvement of peripancreatic lymph nodes. The term Glucagonoma syndrome and glucagonoma are often interchangeably used, but in fact, these are two distinct entities. Glucagonoma syndrome comprises of necrolytic migratory erythema, hyperglucagonemia, diabetes mellitus, anemia, weight loss, glossitis, diarrhea, venous thrombosis and neuropsychiatric disturbances in the presence of a glucagon-producing tumor of the pancreas. Tumors secreting glucagon can occur without the glucagonoma syndrome. The glucagonoma secretion depends on the expression of protein convertase enzyme PC1/3 or PC2 within the tumor itself. As a result of this expression, the clinical manifestations can be variable. The tumor can either present with hyperinsulinemic hypoglycemia in a patient with a previous history of diabetes or with the features of the glucagonoma syndrome. In cases where a tumor is localized surgery is the curative treatment. Reduction of the tumor bulk, removal of the primary by surgery and targeted therapy for the hepatic metastases are the favored approach even when there is the metastasis

Acceptance and commitment therapy for public speaking anxiety: A self-help format

A non-concurrent multiple baseline design across eight participants was used to determine whether working through Hayes and Smith's (2005) book would help those with public speaking anxiety. Hayes and Smith (2005) is based on Acceptance and Commitment Therapy. It encourages people to accept internal experiences as opposed to avoiding and struggling with them. For the purposes of this study, the book was divided into nine components, which participants discussed with the researcher. They also completed measures daily, during baseline and over the intervention period, as well as a battery of tests pre-baseline, mid and post intervention. The multiple baseline data showed that self-reported willingness to approach public speaking situations increased while self-reported avoidance decreased over the intervention. The pre and post measures also showed avoidance of internal experiences decreased significantly after the intervention. These outcomes are in line with changes suggested to result from engaging in such a therapy. The pre and post results also showed that quality of life increased significantly from mid to post-intervention. However, engagement with values did not change. While this measure is expected to change after such an intervention, this result may have occurred because the ideas about values were introduced last in the book. The intervention also led to significant decreases in anxiety, significant changes in thoughts about public speaking and significant increases in anxiety control as shown by the test battery. These findings are positive but are not predicted by processes posited for this therapy. However, there was no control group so these pre vs post comparisons must be interpreted with caution. Despite this limitation, the results suggest that the book, together with therapist contact, can help those with public speaking anxiety

Evaluating Methods for Optimizing Classification Success From Otolith Tracers for Spotted Seatrout (\u3ci\u3eCynoscion nebulosus\u3c/i\u3e) in the Chesapeake Bay

Identifying the natal sources of fish is an important step in understanding its population dynamics. Adult recruits are often sourced from multiple nursery areas, with good quality locations contributing disproportionately more fish to the adult stock. Because population persistence is strongly influenced by nursery habitat, methods that correctly identify the source of recruits are necessary for effective management. Within the last decade, otolith chemistry signatures have been increasingly used as a natural marker to delineate fish from a mixture of nursery sources. Despite the widespread use of otolith trace element and stable isotope ratios as habitat markers, the statistical approaches to handle these data have been slow to develop. Limited guidelines have been offered for constructing the discriminatory function in terms of the number of chemical variables used, the information conveyed by each variable, and the overall stability of important variables with time. Almost all studies argue that juvenile signatures must be collected anew each year at considerable expense. In this study, Rao\u27s test for additional information was used to identify the most useful discriminatory variables for identifying the nursery seagrass habitats for spotted seatrout (Cynoscion nebulosus) in Chesapeake Bay. Additionally, Akaike information criterion (AIC) and Bayes information criterion (BIC) were used to select the discriminant function analysis (DFA) model that minimized the prediction error for determining provenance of adult fish. The AIC technique was also used to construct a short-term multi-year habitat tag for the Bay. Variable selection using Rao\u27s test show that classification accuracy was heavily dependent on the type and number of variables used in the model. Barium was the most important variable and it was the most stable variable over time. From the AIC model selection, adult fish were correctly assigned to nursery area with over 94% accuracy within-year, while the AIC multi-year tag accurately identified the source of historical collections of adult fish with over 80% classification accuracy. These results show that by using correct statistical approaches to construct the discriminatory model, the probability of misclassification for subsequent survivors is minimized. Additionally multi-year models can be developed, directing research for other species